This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary aim is to develop a hyperpolarized (HP) 129Xe MRI-based method to study three dimensional pulmonary gas exchange in vivo. This method will exploit the large chemical shift range of 129Xe and the reasonably high solubility of xenon in tissues to differentially image the uptake of gas-phase, alveolar 129Xe by both the pulmonary blood/gas barrier tissue and red blood cells. Before reaching the red blood cells, HP 129Xe must first diffuse across the barrier tissue. Since diffusive transport times scale with the barrier thickness squared, 129Xe MR is capable of detecting barrier thickness changes as small as several microns. The initial stages of this work will focus on developing 3D gas exchange imaging capabilities. These efforts may involve constructing a gas exchange phantom that produces 129Xe NMR spectra that are similar to those observed in vivo before performing experiments with health controls. Following the development of 3D imaging capabilities, gas exchange in the healthy controls will be compared with well-known small animal models of pulmonary diseases involving gas exchange abnormalities such as fibrosis.